Gefitinib

446.90200

446.90

S65743JHBS

759856|715055

DTXSID8041034

C1855

L01XE02|L - Antineoplastic and immunomodulating agents

29143900

68.74000

4.1

1.322g/cm3

194-198 °C

586.8ºC at 760 mmHg

308.7ºC

1.621

H2O: Sparingly soluble (

0mmHg at 25°C

5.4 and 7.2

NONH for all modes of transport

3

R36/37/38

S24/25; S36; S26

HP1149700

Xi

P301 + P312 + P330-P305 + P351 + P338

H302-H315-H319-H335

|Danger|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P310, P314, P321, P330, P332+P313, P362, P391, P405, and P501|Aggregated GHS information provided by 50 companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m2 (about 80 times the recommended clinical dose on a mg/m2 basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of overdose include diarrhea and skin rash.

In large early clinical trials, elevations in serum aminotransferase levels occurred in 9% to 13% of patients treated with standard doses of gefitinib, and 2% to 4% of patients had to stop therapy because of elevations above 5 times the upper limit of normal. Serum enzyme elevations typically arise after 4 to 12 weeks of treatment with a hepatocellular pattern. Immunoallergic and autoimmune features have not been described, but rash is common in patients receiving gefitinib. Most cases of liver injury due to gefitinib in the literature have been minimally or not symptomatic, and the injury resolved within 1 to 2 months of stopping the drug. Restarting therapy was usually but not always followed by rapid recurrence of serum enzyme elevations, and corticosteroid therapy did not appear to prevent this recurrence. In some instances, lower doses were tolerated with minimal or no ALT elevations. Periodic monitoring of liver tests during therapy is recommended. Despite the frequency of serum aminotransferase elevations during gefitinib therapy, cases of clinically apparent liver injury with jaundice are rare. Cases of severe and fatal hepatotoxicity have been reported to the sponsor and monitoring of liver tests during therapy is recommended.

90% primarily to serum albumin and alpha 1-acid glycoproteins (independent of drug concentrations).

For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.|FDA Label|Gefitinib Mylan is indicated as monotherapy for the treatment of adult patients with locally advanced or metastatic non‑small cell lung cancer (NSCLC) with activating mutations of EGFR‑TK.|Iressa is indicated for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer with activating mutations of epidermal-growth-factor-receptor tyrosine kinase.|Drug: Gefitinib

Gefitinib is a selective tyrosine kinase receptor inhibitor used in the therapy of non-small cell lung cancer. Gefitinib therapy is associated with transient elevations in serum aminotransferase levels and rare instances of clinically apparent acute liver injury.

Antineoplastic Agents

Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.

Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib.|Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.|1400 L [IV administration]|595 mL/min [IV administration]

Primarily hepatic via CYP3A4. Three sites of biotransformation have been identified: metabolism of the N-propoxymorpholino-group, demethylation of the methoxy-substituent on the quinazoline, and oxidative defluorination of the halogenated phenyl group.|Gefitinib has known human metabolites that include 4-Defluoro-4-hydroxy Gefitinib and O-Desmethyl Gefitinib.

48 hours [IV administration]

Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation.

gefitinib

Human drugs -> Gefitinib Mylan -> EMA Drug Category|Antineoplastic agents, Protein kinase inhibitors -> Human pharmacotherapeutic group|Human drugs -> Iressa -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients